Nadal

Fakultäten » Medizinische Fakultät » Kinderspital Zürich: Medizinische Klinik » Infektiologie, Abteilung » Prof. Dr. David Nadal » Nadal

Completed research project

Title / Titel	Impact of innate immunity in the induction of Epstein-Barr virus-associated B-cell transformation and tumor formation
PDF	Abstract (PDF, 14 KB)
Summary / Zusammenfassung	Lymphoma is one of the most frequent cancers, and the vast majority of cases are of B-cell origin. Several types of lymphoma are linked to the Epstein-Barr virus (EBV), a B-cell tropic g herpes virus that establishes persistent, usually asymptomatic infection in > 95% of humans. EBV transforms B-cells in vitro to lymphoblastoid cell lines, indicating EBV’s potential role in tumor formation in vivo. The switch of latent EBV infection to lytic replication results in death of the infected cell. While a wealth of data has been accumulated from EBV’s impact on host gene expression in vitro and ex vivo, the critical events following primary cellular EBV infection and during the process leading to EBV-induced transformation remain elusive. Recent data suggest that components of the innate immune system such as Toll-like receptor 9 (TLR9) may operate in the pathogenesis of lymphomas. The interplay between TLR9 signaling and EBV-induced transformation has not been explored. We hypothesize that triggering of TLR9 induces EBV-associated B-cell transformation and tumor formation. Thus, we aim to explore different ways of EBV inoculation to increase the in vitro EBV infection rate of B cells isolated ex vivo from human tonsils from EBV-negative donors to subsequently investigate the course of infection from shortly after cellular EBV invasion till transformation in a pure target cell population. The proposed project will elucidate the EBV and B-cellular prerequisites for increased EBV infection in vitro and establish tools for the subsequent study of molecular mechanisms of EBV gene expression and responses to TLR9 triggering or inhibition in in vitro and in vivo models and lymphoproliferative lesions from patients.
Keywords / Suchbegriffe	Epstein-Barr virus, inate immunity, tumor formation, lymphoma, cell transformation,
Project leadership and contacts / Projektleitung und Kontakte	Prof. Dr. med. David Nadal, MD (Project Leader) david.nadal@kispi.uzh.ch PD Dr. med. Roberto Speck, MD roberto.speck@usz.ch Prof. Dr. Beat Schaefer, PhD beat.schaefer@kispi.uzh.ch PD Dr. med. Michael Kurrer, MD michael.kurrer@usz.ch
Funding source(s) / Unterstützt durch	SNF (Personen- und Projektförderung)
Duration of Project / Projektdauer	Apr 2007 to Mar 2010